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The objective of the study was to compare compliance with and the hypocholesterolaemic effect of lovastatin given once daily as a morning or an evening dose. Twenty-four out-patients with familial hypercholesterolaemia were randomly assigned to receive placebo first, then lovastatin 20 mg, to be taken once daily for 4 weeks, either with the breakfast or evening meal, in a single-blind fashion. Drug compliance was assessed by pill counts and continuous electronic monitoring. Two compliance parameters were evaluated, consumption, defined as percentage of prescribed doses taken, and time compliance, the percentage of total dosing events recorded within defined intervals (6.00-10.00 h, and 17.00-21.00 h), for the morning and evening regimes. Both regimes satisfactorily reduced the total and LDL-cholesterol concentrations, and there was no significant difference in the extent of the reductions. Pill counts overestimated compliance, as revealed by the monitoring method. The times of actual consumption of doses by the patients often differed from that prescribed, predominantly in patients who were told to take the evening dose. Partial time compliance may have confounded the efficacy of the drugs. Electronic compliance monitoring appears to be particularly useful in chronopharmacological studies.

The long-term effect of a low-fat diet and physical training was investigated in 36 men (mean age 51 +/- 6 years) with coronary heart disease (one-vessel disease, n = 11; two vessel-disease: n = 18; three-vessel disease: n = 7). 18 patients (interventionist, group 1) undertook physical training within a coronary sport group (1 h twice weekly) and daily bicycle ergometry (30 min). They were held to a low-fat diet. In the remaining 18 patients (control, group 2), physical training and low-fat diet depended on own initiative after receiving advice. Over an observation period of 6 years total cholesterol concentration in the 17 patients of group 1 decreased significantly (243 +/- 33 vs. 219 +/- 28 mg/dl; P0.02). Physical performance in 12 patients (group 1) increased from 169 +/- 40 to 202 +/- 42 W in (P0.01). In contrast, total cholesterol increased slightly in group 2 (n = 16) from 245 +/- 31 at the beginning to 247 +/- 39 mg/dl (no significant change) at the end of the 6 years. Physical performance (n = 12) decreased slightly from 165 +/- 45 to 146 +/- 52 W (not significant). The difference between the two groups was significant after 6 years (P0.02 and P0.007, respectively). There seemed to be a tendency for progression of the coronary heart disease to be slower in the interventionist than the control group.

The composition of fasting gallbladder bile was investigated in a group of 14 healthy men both on their normal diets and on a low cholesterol diet containing less saturated and more polyunsaturated fat given twice for 4 weeks. These dietary changes caused a 21.6% reduction of total serum cholesterol levels. With the use of the fat-modified diet lithogenic indices of fasting gallbladder bile were not significantly changed despite increased relative concentrations of bile acids and decreased relative concentrations of phospholipids and cholesterol in bile. Thus, the experiment provided no evidence for an increased cholelithiasis risk in healthy men ingesting 'prudent diets'.

The acute and subacute effects of different diets on serum high density lipoprotein (HDL) cholesterol concentration and/or HDL composition are described. In obese normolipemic, hypercholesterolemic (type II) and hypertriglyceridemic (type IV) patients, low HDL cholesterol values remained low during total starvation for 2 weeks. Prudent diets in patients with type II and IV hyperlipoproteinemia had no significant effects on HDL cholesterol within 3 weeks, whereas in normal individuals, a high carbohydrate diet given for 10 days caused significant decreases in HDL cholesterol with concomitant increases in HDL triglycerides as compared to a high-fat diet. The HDL triglyceride fatty acid composition changed in healthy volunteers during the day, depending on the type of ingested fat. The data demonstrate the possibility of acute manipulations of HDL in normal patients and the difficulties of normalizing low HDL cholesterol levels in patients by dietary means. Additional information on the function of HDL is desirable before the therapeutic manipulation of HDL cholesterol or other constituents of HDL can be evaluated regarding their effectiveness in the prevention of ischemic vascular disease.

A two-step procedure for the microdetermination of cholesterol in serum lipoproteins is compared with cholesterol quantitation after density gradient ultracentrifugation. Serum lipoproteins from 10 mul of serum are separated by electrophoresis on agarose and visualized by precipitation with dextran sulfate--CaCl2. The lipoprotein bands are cut off from the plates, the agarose slices are hydrolyzed by gas-liquid chromatography. The comparison between the two procedures reveals satisfactory correlations for beta-and pre-beta-lipoproteins and total serum. There is excellent recovery of cholesterol in fractionated lipoproteins.

In the present investigation 238 randomly selected male individuals of the general population (age 19--41 years) and 42 age-matched male patients with recurrent renal stone formation (calcium oxalate and/or calcium phosphate) were studied under outpatient conditions without dietary restrictions. Urinary Na excretion was 207 +/- 82 mmol/24 h (range 55--570) in controls and 208 +/- 100 (range 76--575) in recurrent renal stone formers. Both in controls (r = 0.36; p less than 0.01) and in stone formers (r = 0.4; p less than 0.01) a significant correlation was observed between urinary excretion of sodium and calcium. Urinary sodium excretion was unrelated to systolic or diastolic blood pressure in normotensive or hypertensive individuals. This finding indicates that factors other than sodium are involved in the maintenance of hypertension. Urinary sodium, presumably an index of intake of nutrients, was significantly correlated to several coronary risk factors, e.g. fasting glucose, cholesterol and overweight. There existed a significant inverse relationship between fasting plasma phosphate and urinary sodium, but not between fasting plasma phosphate and serum iPTH or urinary cAMP. This finding points to some function of sodium excretion as one determinant of plasma phosphate.

The effect of a 4-week treatment with 600 mg/day of bezafibrate in addition to a low-cholesterol, fat-modified diet on plasma lipids and lipoproteins and on biliary lipids and fecal sterols was investigated in 12 healthy men aged 25–39, and compared to the effect of the diet plus placebo, using a double-blind crossover design. The comparison of placebo and treatment values indicated that bezafibrate, beyond the effect of the diet, significantly lowered concentrations of circulating triglycerides (−25.5%), total cholesterol (−25.8%), LDL cholesterol (−19.5% ), and apolipoprotein B (−19.9% ), and increased apolipoprotein A-II concentrations in serum (+15.0%). There was a tendency towards lower biliary bile acid and cholesterol secretion rates with bezafibrate; lithogenic indices in fasting and stimulated bile were similar with the drug and placebo. Fecal bile acid excretion rate with diet plus bezafibrate was significantly less than with diet plus placebo. The data obtained are in accord with the hypothesis that bezafibrate exerts its effects on cholesterol and bile acid metabolism predominantly by decreasing VLDL secretion, possibly through an enhancement of fatty acid β-oxidation in the liver.

The previously described procedure of direct determination of LDL-cholesterol after selective extraction of VLDL and HDL with polycations and a polycation-exchange resin has been improved by using dodecoylated poly(ethyleneimine) instead of poly(ethyleneimine). The acyl derivative has a higher affinity for lipoproteins. Disc-electrophoretic patterns of lipoproteins separated by this procedure correspond to patterns of apolipoproteins in VLDL and HDL, a finding that corroborates the conclusion that the mechanism of the selective binding of certain lipoproteins to lipophilic water-soluble polycations is based on hydrophobic interaction between the polymer and lipids located at the surface of lipoprotein particles. The procedure offers a simple possibility for direct LDL-cholesterol and LDL-triglyceride determination and for the isolation of VLDL and HDL. The mechanism of the reaction has a biochemical correlate in the action of phospholipase A2 on phospholipids.

The effect of guar (15.6 g/day), a dietary fibre, and simultaneous administration of bezafibrate (600 mg/day) during dietetic treatment on the plasma lipoproteins and apolipoproteins was investigated in 12 patients with familial hypercholesterolemia (corresponding to the HLP type IIa pattern). Either bezafibrate alone or bezafibrate in combination with guar was administered in a cross-over study for 3 months. Guar led to an additional lowering of the total cholesterol in the plasma by 7% (P less than or equal to 0.05) associated with a fall of the low density lipoprotein cholesterol (LDL-cholesterol (LDL-cholesterol) by 13% (P less than or equal to 0.01) without any changes in the very low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterols. In parallel with the decrease in LDL-cholesterol, the apoprotein B also was diminished by 20% (P less than or equal to 0.05). The plasma triglyceride level and the triglyceride distribution within the individual lipoprotein fractions were not altered in any consistent manner by the addition of guar. Neither the fasting plasma glucose level nor the body weight were affected. The side-effects due to guar treatment consisted of slight nausea, meteorism and constipation, but this did not in any of the cases lead to early termination of the study. These results demonstrate that guar exerts its cholesterol-lowering effect in addition to that of bezafibrate.

The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 [69 to 304] mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and "usual medical care" was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress.

In a 60-year-old patient with manifest diabetes mellitus and in his 63-year-old brother with latent diabetes mellitus hypobeta-lipoproteinaemia was diagnosed. Cholesterol values were around 1,8 mmol/1 in whole serum samples. The LDL-cholesterol fraction was 1,04 mmol/1. The beta-lipoprotein band in the lipoprotein electrophoresis was markedly reduced. Apolipoprotein B measured by radial immuno-diffusion was about 30% of the normal for age. The components of LDL were normal. Values of hepatic triglyceride lipase and lipoprotein lipase in heparinised plasma were within the normal range. The simultaneous occurrence of hypobetalipoproteinaemia and diabetes mellitus is described here for the first time.

The effect of beta-sitosterol on plasma lipids and lipoproteins was evaluated in a randomized double-blind cross-over trial in 15 children and adolescents with familial hypercholesterolemia over a period of 6 months. Twelve patients completed the study, with good adherence to drug intake. Sitosterol lowered the plasma total choelsterol by 6%, LDL cholesterol by 7% and HDL cholesterol by 15% (P less than 0.05). This insufficient response of total and LDL cholesterol and the marked fall of HDL cholesterol appears to advise against the use of beta-sitosterol granulate in juvenile type II hyperlipoproteinemia.

The effect of nicotinic acid and several derivatives on the nocturnal level of free fatty acids was studied in 12 healthy young women and men. Free fatty acids are an important precursor of plasma triglycerides and their concentration is highest at night. The drugs used were nictinic acid, beta-pyridyl-carbinol, mesoinositol hexanicotinate and xantinol nicotinate. The highest plasma nicotinic acid level was observed with beta-pyridyl-carbinol, but significant reduction in free fatty acids during the entire night was only achieved with inositolhexanicotinate and xantinol nicotinate. There was no correlation between the plasm levels of free fatty acids and nicotinic acid at any sampling time. If prolonged reduction in free fatty acid concentration is desired in the therapy of hyperlipidemias, the inositol and xantinol esters of nicotinic acid appear to be superior to the other preparations.

Because the incidence of venous thromboembolism, coronary heart disease, and stroke is increased in users of oral contraceptives (OCs), the possible causal metabolic side effects of OCs have been widely investigated. In this article we present epidemiologic data associated with OC use. Total plasma triglycerides and cholesterol levels were elevated in OC users while high-density lipoprotein cholesterol levels were lowered. Another section discusses some hormone-dependent physiologic and pathophysiologic aspects of lipid metabolism. Finally, we report on the isolated influence of estrogens and progestogens and their interrelation, including some recent findings about the effects of different progestogens on lipoproteins.The incidence of venous thromboembolism, coronary heart disease, and stroke is increased in users of oral contraceptives (OCs). This article presents epidemiologic data associated with OC use. In a health and nutrition survey of 800 women (20-40 years of age) from Heidelberg, West Germany, fasting blood values, 24-hour urine values, blood pressure readings, fat biopsies, and data on nutritional and medication intakes were recorded. Comparisons were made between current OC users, former users, and those who had never used the pill. Total plasma triglycerides and cholesterol levels were elevated in OC users while high density lipoprotein cholesterol levels were elevated in OC users while high density lipoprotein cholesterol levels were lowered. The epidemiologic experience with users of OCs showed an association between the estrogen content of the pill and venous thromboembolism; therefore, the estrogen dose was lowered. In the low-estrogen OC, significant positive correlations of arterial disease and hypertension with the progestogens content of the pill were noted. There are differences between effects of exogenous and endogenous gonadal hormones in men and women and between single or combined treatment with estrogens and progestogens. Beneficial effects on some lipoproteins can possibly be elicited with certain progestogens. Postmenopausal women might profit from estrogen therapy.

The previously described procedure of direct determination of LDL-cholesterol after selective extraction of VLDL and HDL with polycations and a polycation-exchange resin has been improved by using dodecoylated poly(ethyleneimine) instead of poly(ethyleneimine). The acyl derivative has a higher affinity for lipoproteins. Disc-electrophoretic patterns of lipoproteins separated by this procedure correspond to patterns of apolipoproteins in VLDL and HDL, a finding that corroborates the conclusion that the mechanism of the selective binding of certain lipoproteins to lipophilic water-soluble polycations is based on hydrophobic interaction between the polymer and lipids located at the surface of lipoprotein particles. The procedure offers a simple possibility for direct LDL-cholesterol and LDL-triglyceride determination and for the isolation of VLDL and HDL. The mechanism of the reaction has a biochemical correlate in the action of phospholipase A2 on phospholipids.

The effect of beta-sitosterol on the lipid and lipoprotein level was evaluated in a randomised double-blind cross-over trial in 24 patients with primary familial type II hyperlipoproteinaemia over a period of 16 weeks. All patients completed the trial, however 10 of them had to be excluded from the evaluation due to fluctuations of their body weight or unreliable drug intake. Sitosterol lowered the total cholesterol level by 12.5% (P less than 0.01) from 9.96 mmol/l (3.69 g/l) to 8.37 mmol/l (3.23 g/l). The LDL-cholesterol level was lowered by 19.5% (P less than 0.05). The sitosterol concentration in plasma was consistently lower than 0.3% of total cholesterol. No side effects or tachyphylaxis was observed in the course of the trial. A return to normal of an increased serum cholesterol level by a combination of a lipid lowering diet and sitosterol monotherapy was only achieved in one patient.

The effect of typical fat-modified diets on serum lipids, lipoproteins and apolipoproteins, on the intravenous fat-tolerance test and on fecal sterol excretion were observed in a group of men living at home and compared to that of their normal diets. Two 4-week-long diet periods alternated with four periods of 6 weeks' duration during which the men followed their normal dietary habits and accustomed life-styles. According to a randomized cross-over design sunflower oil and corn oil were used as the main fat sources for the fat-modified diets. Both diets lowered total cholesterol considerably acting mainly on LDL cholesterol, without affecting plasma triglycerides significantly. Apolipoprotein A-I and A-II concentrations in serum remained constant, and clearance of triglyceride-rich lipoproteins, as measured by an intravenous fat-tolerance test (Intralipid test), was not significantly affected. While changes of all measured parameters pointed in the same direction, serum total and LDL cholesterol levels were significantly lower with corn oil than with the sunflower oil. Excretion of endogenous sterols (fecal sterol balance) was higher with the fat-modified than with the normal diet. This increase in sterol excretion closely corresponded to the extent of serum cholesterol lowering.

Hypocholesterolemia (less than 120 mg/dl) was found in 200 out of 3,700 patients admitted consecutively to a University Department of Internal Medicine. In 91, hypocholesterolemia as defined above could be confirmed in a second serum sample on the following day. Mortality during hospitalization in this group was 32%. When diagnoses were grouped into 5 categories, prognosis was particularly poor in heart (36%) and liver disease (31%) and in malignancies (33%), while patients with malabsorption syndromes had a considerably better prognosis (10% mortality). Hypocholesterolemia was associated with a low cholesterol/phospholipid ratio and may be among the first signs of further deterioration of disease.

The differential effect of two diets, taken in synchrony with the menstrual cycles for 2 wk each,on serum and bilelipidswas investigated inyoung healthywomen. The "normal" diet was high in cholesterol and total fat, and low in polyunsaturated fat and fiber, the "prudent" diet contained a high proportion of polyunsaturated fat and fiber, but was low in cholesterol and total fat; there was little difference inenergycontent. Both in whole serum and in low-density lipoprotein the concentrations of cholesterol and apolipoprotein B were almost 30% lower with the "prudent" than with the "normal" diet; HDL-cholesterol was 16.3% lower. Triglycerides were increased, only in the very-low-density lipoproteins while cholesterol and apolipoprotein B did not change much in this fraction. The risk to acquire cholesterol gallstones was not less with the use of the "prudent" diet as originally expected. While using the "prudent" diet five of the women had slightly higher lithogenic indices, in two there were much higher values (>25%), and only in three the lithogenic index was unchanged or slightly lower than with the "normal" diet. Am J ClinNuir 1985:42:1201-1205.

Diurnal lipid and lipoprotein profiles were measured in 28 healthy volunteers after 10-day treatment periods with placebo, bezafibrate (200 mg 3-times daily) or clofibrate (500 mg 3-times daily) in a double-blind, parallel trial. The two drugs lowered fasting triglyceride and cholesterol levels (p less than or equal to 0.05 for cholesterol with bezafibrate vs placebo). Diurnal triglyceride profiles were lowest with bezafibrate due to lowest fasting triglycerides. Alimentary lipaemia with placebo was mild and due to increased VLDL-triglycerides, while the other lipoprotein lipids and total plasma cholesterol remained virtually unchanged during the day. Bezafibrate (half-life 2 hours) and clofibrate (half-life 15 hours) gave similar diurnal triglyceride patterns. The diurnal values were dependent on the fasting values. Changes in the cholesterol/phospholipid ratio during the day may be related to altered post-prandial composition of HDL.

The efficacy of a fat-modified, low-cholesterol diet was studied in 38 children and adolescents with familial hypercholesterolemia on an out-patient basis, and the results compared with those achieved with dietary treatment in hospital. On an out-patient basis, a 10% reduction of plasma cholesterol levels was achieved and maintained. However, no patient showed normalization of plasma cholesterol levels. During hospitalisation, the mean plasma cholesterol levels fell by 24%, beta-cholesterol levels by 27%. This resulted in normal plasma lipids in almost half of the patients. Our results demonstrate the efficacy of intensive dietary management in children and adolescents with familial hypercholesterolemia. Long-term results on an out-patient basis could probably be improved by early nutrition education and an improved supply of suitable dietary foods.

The effects of Acipimox (5-methylpyracine-2-carboxylic acid-4-oxide, 3 X 250 mg/day) on plasma lipids, lipoproteins, and biliary lipids were studied in 14 healthy male volunteers using a double blind cross-over design. There was a significant (P less than 0.05) rise of HDL-cholesterol by 9.8%, while effects on other lipids and lipoproteins were small and insignificant (total cholesterol minus 6.5%, LDL-cholesterol minus 11.8%, free cholesterol minus 4.2%, total triglycerides plus 13.5% and phospholipids plus 3.9%). There was a significant rise of the HDL-cholesterol/LDL-cholesterol ratio by 23.6% (P less than 0.02) and of the HDL-cholesterol/total cholesterol ratio by 16% (P less than 0.05). Apolipoproteins AI, AII, and B were not significantly affected. The ratio of HDL-cholesterol/Apo AI increased significantly (P less than 0.05), and the ratio of HDL-cholesterol/Apo AII rose from 1.22 to 1.32 (P less than 0.05), while the ratio LDL-cholesterol/Apo B fell from 1.96 to 1.73. The composition of HDL and LDL, therefore, must have been altered by Acipimox. The relative cholesterol concentration in bile was significantly (P less than 0.05) increased by treatment with Acipimox, while bile acids and phospholipids were not significantly affected. The lithogenic index rose significantly by 15.1% (P less than 0.02) as calculated according to Admirand and Small, while calculations according to Hegard and Dam yielded a slight insignificant rise (P less than 0.1). The findings suggest that treatment with Acipimox might be associated with an increased risk of cholelithiasis. However, only long-term epidemiologic studies can ultimately demonstrate whether or not Acipimox increases the risk of gallstone formation.

The effects of a combined exercise and low-fat dientary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to “ideal” levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize midly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.